Analysis of genetic and clinical characteristics of Charcot-Marie-Tooth disease patients caused by ARSs gene variation
LI Yi-qing
LI Gui-he
CAO Chun-yan
GAO Yuan
CHEN Wan-jin
HE Jin
Abstract：Objective To summarize the clinical manifestations and genetic characteristics of patients with Charcot-Marie-Tooth disease(CMT)caused by ARSs gene variation.Methods and Results A total of 12 probands with clinical diagnosis of CMT were selected from The First Affiliated Hospital of Fujian Medical University from January 1997 to February 2024 and included in the clinical registration cohort of the hospital.Clinical symptoms:10 patients had normal proximal limb muscle strength,while the distal limb muscle strength was seriously involved.Most muscular atrophy occurred below ankle joint and wrist joint.Two patients had subjective numbness of limbs,and one patient had reduced symmetry sensation on superficial sensory examination.Tendon reflexes were normal in only one patient.EMG characteristics:for the 11 probands,the median nerve motor nerve conduction velocity(MNCV)ranged from 0 to 65.70 m/s,with an average of 36.67 m/s,and the median nerve compound muscle action potential(CMAP)ranged from 0 to 19.50 mV,with an average of 5.42 mV.ARSs gene variation analysis:there were 4 ARSs gene variants,including GARS1,YARS1,AARS1 and SARS1.Among the 8 GARS1 gene mutation sites(c.1235G>A,c.598G>C,c.362G>A,c.1415A>G,c.637C>T,c.374A>G,c.722G>T,c.1000A>T),c.598G>C and c.722G>T had not been reported at home and abroad.EMG showed 5 probands were intermediate CMT(ICMT)and 3 were CMT2.Among the 2 YARS1 gene mutation sites(c.1333A>G,c.787T>C),C.787T>C has not been reported at home and abroad,and the 2 probands were CMT1 and ICMT.One proband with AARS1 gene mutation(c.896C>T),the EMG showed CMT2;and there was one proband with SARS1 gene mutation(c.1187C>T),and the EMG showed ICMT.Conclusions CMT caused by ARSs gene variation mainly causes hereditary motor neuropathy with or without sensory involvement,and the main clinical phenotypes are CMT2 and ICMT.Different ARSs gene variation-related CMT patients have different clinical manifestations,and gene detection should be performed to confirm the diagnosis.The genetic spectrum of CMT was expanded to provide a basis for disease diagnosis and genetic counseling.
Keywords：Charcot-Marie-Tooth diseaseAmino acyl-tRNA synthetasesGenesMutationPhenotypePedigree
Publication Date：2025-07-25
Online Publishing Date：2025-08-28(First online date of this platform, not the publication date of the document)
Pages：7( 622-628 )